125.9, 126.4, 126.7, 127.0, 128.3, 128.5, 128.9, 134.4, 134.7, 139.4. Anal. Calcd for

Ci8H20N2: C, 81.78; H, 7.63; N, 10.60. Found: C, 81.52; H, 7.37; N, 10.65.

3.4.4 General Procedure for the Preparation of Benzotriazolvl Intermediates 3.13 and
3.14a-c.

 Using the same procedure as for the preparation of 3.12a-c, reaction of 3.10a with

benzotriazole and aqueous formaldehyde (1 or 2 equiv) led to 3.13.

 (2S)-2-[(1H-1,2,3-Benzotriazol-1-ylmethyl)amino]-N-(4-methylphenyl)-3-

phenylpropanamide (3.13): white microcrystals (from CH30H); yield, 92%; mp

136-137 OC; [a]25D = -74.5 (c 1.76, CHC13); 1H NMR 6 2.32 (s, 3H), 2.70 (br s, 1H),

2.79 (dd, J= 13.8, 8.7 Hz, 1H), 3.01 (dd, J= 14.1, 4.8 Hz, 1H), 3.61 (dd, J= 8.4, 4.5 Hz,

1H), 5.41-5.53 (m, 2H), 6.87-6.89 (m, 2H), 7.08-7.14 (m, 5H), 7.33-7.40 (m, 4H), 7.44

(d, J= 7.8 Hz, 1H), 8.04 (d, J= 8.7 Hz, 1H), 8.67 (s, 1H); 13CNMR 6 20.8, 39.0, 60.9,

61.3, 108.8, 119.7, 120.1, 124.1, 127.0, 127.8, 128.6, 128.7, 129.4, 132.5, 134.1, 134.6,

135.9, 146.0, 170.2. Anal. Calcd for C23H23N50: C, 71.67; H, 6.01; N, 18.17. Found: C,

71.60; H, 6.25; N, 18.29.

 A mixture of 3.10a-c (2.0 mmol), BtH (0.48 g, 4.0 mmol) and paraformaldehyde

(0.18 g, 6.0 mmol) withp-TsOH'H20 (0.08 g, 0.4 mmol) was stirred in refluxing benzene

(25 mL) using a Dean-Stark apparatus for 2 h. After cooling, benzene was evaporated and

toluene (25 mL) was added, and then the mixture was refluxed for another 1 h. The

mixture was washed with 2 M NaOH. The aqueous phase was extracted with EtOAc and

the combined organic phase was washed with water, brine, and dried over anhyd K2CO3.

Removal of solvent under reduced pressure gave crude 3.14a-c, which were used directly

for the subsequent reactions. Attempt to purify 3.14a-c failed due to their significant

decomposition on silica gel.